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[器官移植中HLA相容性的新进展]

[New aspects of HLA compatibility in organ transplantation].

作者信息

Snanoudj Renaud, Legendre Christophe

机构信息

Service de néphrologie-transplantation, hôpital Necker, Assistance publique-Hôpitaux de Paris, 149, rue de Sèvres, 75015 Paris, France; Université Paris Descartes, Sorbonne Paris Cité, 12, rue de l'École-de-Médecine, 75006 Paris, France.

Service de néphrologie-transplantation, hôpital Necker, Assistance publique-Hôpitaux de Paris, 149, rue de Sèvres, 75015 Paris, France; Université Paris Descartes, Sorbonne Paris Cité, 12, rue de l'École-de-Médecine, 75006 Paris, France.

出版信息

Nephrol Ther. 2016 Apr;12 Suppl 1:S125-30. doi: 10.1016/j.nephro.2016.01.006. Epub 2016 Mar 8.

Abstract

In organ transplantation, HLA compatibility between a donor and a recipient is currently assessed through the comparison of their HLA antigens and the sole count of incompatible HLA antigens. Similarly, antibodies were originally described as antigenic-specific. With solid phase assays detection of anti-HLA antibodies and crystallographic studies, it is now recognized that anti-HLA antibodies are not specific for antigens, but for epitopes, i.e. short polymorphic sequences of amino acids that are more often in positions accessible to allo-antibodies. These epitopes, due to the distribution of HLA molecules polymorphism, may be shared by different HLA antigens. This explains why an immunization towards a given HLA antigen can lead to synthesis of antibodies reactive towards other antigens sharing one or more epitopes. Similarly, structural comparison of the HLA molecules of a recipient and his donor defines the epitope load, i.e. the number of incompatible epitopes. This epitope load is correlated with the risk of developing antibodies specific for the donor after transplantation. New tools, such as the HLAMatchmaker software, allow to determine the epitopic load and to analyze the epitopic specificity of alloantibodies. These tools will possibly lead to rethink the method of graft allocation, or at least to take differently into account HLA compatibility in allocation algorythms.

摘要

在器官移植中,目前通过比较供体和受体的人类白细胞抗原(HLA)抗原以及对不相容HLA抗原进行单纯计数来评估两者之间的HLA相容性。同样,抗体最初被描述为具有抗原特异性。随着固相检测抗HLA抗体以及晶体学研究的开展,现在人们认识到抗HLA抗体并非对抗原具有特异性,而是针对表位,即氨基酸的短多态性序列,这些序列更常位于同种异体抗体可及的位置。由于HLA分子多态性的分布,这些表位可能会被不同的HLA抗原共享。这就解释了为什么针对某一特定HLA抗原的免疫反应会导致合成出对共享一个或多个表位的其他抗原具有反应性的抗体。同样,受体与其供体的HLA分子的结构比较可确定表位负荷,即不相容表位的数量。这种表位负荷与移植后产生针对供体的特异性抗体的风险相关。新的工具,如HLAMatchmaker软件,可用于确定表位负荷并分析同种异体抗体的表位特异性。这些工具可能会促使人们重新思考移植物分配方法,或者至少在分配算法中以不同方式考虑HLA相容性。

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